title: TULP1 mutation in two extended Dominican kindreds with autosomal recessive retinitis pigmentosa.
abstract: The RP14 autosomal recessive Retinitis pigmentosa (arRP) locus has been mapped to a 2cM region of chromosome 6p21.3. TULP1 (the gene encoding tubby-like protein 1) is a candidate target for the disease mutation because it maps to the RP14 minimum genetic region and because a mutation in the highly homologous mouse tub gene leads to obesity, deafness and early progressive retinal degeneration. Here we report a splice-site mutation (IVS14+1, G-->A) that is homozygous in all affected individuals (N=33) and heterozygous in all obligate carriers (N=50) from two RP14-linked kindreds. The mutation was not observed in 210 unrelated controls. The data indicate that impairment of TULP1 protein function is a rare cause of arRP and that the normal protein plays an essential role in the physiology of the retina.
authors.affiliation: Department of Genetics & Development, College of Physicians and Surgeons at Columbia University and New York State Psychiatric Institute, New York 10032, USA.
authors.forename: P
authors.initials: P
authors.lastname: Banerjee
authors.forename: P W
authors.initials: PW
authors.lastname: Kleyn
authors.forename: J A
authors.initials: JA
authors.lastname: Knowles
authors.forename: C A
authors.initials: CA
authors.lastname: Lewis
authors.forename: B M
authors.initials: BM
authors.lastname: Ross
authors.forename: E
authors.initials: E
authors.lastname: Parano
authors.forename: S G
authors.initials: SG
authors.lastname: Kovats
authors.forename: J J
authors.initials: JJ
authors.lastname: Lee
authors.forename: G K
authors.initials: GK
authors.lastname: Penchaszadeh
authors.forename: J
authors.initials: J
authors.lastname: Ott
authors.forename: S G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: T C
authors.initials: TC
authors.lastname: Gilliam
mesh_terms: D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D017931:DNA Primers; D004293:Dominican Republic; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006580:Genetic Carrier Screening; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012174:Retinitis Pigmentosa / Q000235:genetics*
chemical_list: D017931:DNA Primers; D005136:Eye Proteins; C105443:TULP1 protein, human; C491353:Tulp1 protein, mouse